Synthesis and Biological Evaluation of Metabolites of 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine (ST1535), A Potent Antagonist of the A2A Adenosine Receptor f

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• 作者：Giovanni Piersanti ; Francesca Bartoccini ; Simone Lucarini ; Walter Cabri ; Maria Antonietta Stasi ; Teresa Riccioni ; Franco Borsini ; Giorgio Tarzia ; Patrizia Minetti
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：July 11, 2013
• 年：2013
• 卷：56
• 期：13
• 页码：5456-5463
• 全文大小：307K
• 年卷期：v.56,no.13(July 11, 2013)
• ISSN：1520-4804

文摘

The synthesis and preliminary in vitro evaluation of five metabolites of the A_2A antagonist ST1535 (1) are reported. The metabolites, originating in vivo from enzymatic oxidation of the 2-butyl group of the parent compound, were synthesized from 6-chloro-2-iodo-9-methyl-9H-purine (2) by selective C鈥揅 bond formation via halogen/magnesium exchange reaction and/or palladium-catalyzed reactions. The metabolites behaved in vitro as antagonist ligands of cloned human A_2A receptor with affinities (K_i 7.5鈥?3 nM) comparable to that of compound 1 (K_i 10.7 nM), thus showing that the long duration of action of 1 could be in part due to its metabolites. General behavior after oral administration in mice was also analyzed.